tbuckley/cabot-search huggingface dataset:
Real-world evidence of first-line pembrolizumab plus chemotherapy in metastatic non-squamous NSCLC: A single-centre experience.
Authors: Subhadeep Bose, Mujtaba Syed Khaja, Asha Siva, Paula Wilson, Helen Grist, Nishanth Murukesh
Journal: Journal of Clinical Oncology (2023)

e21091 Background: Pembrolizumab plus chemotherapy is now the standard of care in previously untreated patients with metastatic non-squamous NSCLC post the results of KEYNOTE 189 trial. This study is to evaluate the real world outcomes and toxicity data in similar subset of patients treated with this protocol in a non-trial setting. Methods: We analysed 38 patients who were treated with Pembrolizumab plus Platinum-Pemetrexed from June 2019 to October 2021. We stratified the patients based on age, performance status, smoking habits, PDL1 results, presence of brain metastases. Our primary endpoint was to collect survival outcome (OS and PFS) and toxicity profile. Baseline patient and disease characteristics were compared using the chi-square test. PFS and OS were calculated by Kaplan-Meier method. Data was analyzed using R version 4.1.1. Results: At a median follow-up of 15.6 (10.35 – 27.33) months, the median PFS was 11.1 months (95% CI 8.31-18.4) and median OS was 15.6 months (95% CI 11-27.3). Median OS at 12 months was 60.3 %(95% CI41.9 – 74.5).63% patients had completed all 4 induction cycles and the median of 7 (1-19) maintenance cycles were given. 63% patients had an objective response to induction chemo (56% PR,7% SD).The main toxicity profiles were fatigue (35%), renal impairment (13%), hepatitis (28%), myelosuppression (13%), rash (18.9%), thyroid problems (24%).Grade 3 diarrhea was seen in 8% and pneumonitis in 2.7%.12 patients stopped treatment due to toxicity. Conclusions: In comparison with the seminal Keynote 189 trial, our median PFS was better (11.1 months vs 9 months), however our 12-month OS rates were worse (60.3 vs 69.2%), however this needs a longer follow-up in relation to maintenance treatment to accurately assess this outcome. In general the tolerance has been at par with the reported trials as is evident from the results.[Table: see text]
Plasma cell leukemia: A multicenter retrospective study of 150 patients.
Authors: Iloabueke Gabriel Chineke, Betsy C. Wertheim, Denise Roe, Ashley Larsen, Douglas W. Sborov, Victoria Vardell, Damian Jonathan Green, Dominique Degraff, Michaela Liedtke, Maire Okoniewski, Mohammed Wazir, Omar Nadeem, Ashley Paquin Shubert, Rebecca Wang Silbermann, Levanto Gershon Schachter, David Coffey, Timothy Martin Schmidt, Matthew Brunner, Sandy Wai Kuan Wong, Krisstina L. Gowin
Journal: Journal of Clinical Oncology (2023)

8014 Background: Despite the use of novel induction regimens, stem cell transplantation (SCT), and maintenance therapy, plasma cell leukemia (PCL) remains a challenging disease with a dismal prognosis. Currently, there is no agreed standard of care management for PCL. We conducted a multicenter retrospective analysis of the clinical presentation, treatment, and outcomes of 150 patients with PCL. Methods: Data of patients diagnosed with pPCL or sPCL between 01/2010 and 01/2021 were entered into a study-specific REDCap database from 7 different U.S. academic sites. PCL was defined as ≥ 5% circulating plasma cells. Clinical data included baseline patient characteristics, clinical presentation, treatment, therapeutic response, and survival outcomes. Overall survival (OS) curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression tested associations between patient characteristics and OS, generating hazard ratios (HR) and 95% confidence intervals (CI), adjusted for PCL type (primary or secondary) and SCT. Results: The analytical cohort included 93 pPCL and 57 sPCL patients. Median age at diagnosis was 60 years. High-risk cytogenetics were found in 56.7% of the patients where it was documented. Of the 79 patients with a documented induction regimen, 58.2% received a proteasome inhibitor triplet, 22.8% received a VTD-Pace like conventional chemotherapy, and 3% received a daratumumab quadruplet regimen. SCT (autologous or allogeneic) was done in 56.1% of the patients. The median OS for all patients, those with pPCL, and those with sPCL was 20.3, 36.6, and 3.2 months, respectively. Secondary PCL was associated with worse survival outcomes compared with pPCL (HR, 2.46; 95% CI, 1.51-3.98; p&lt;0.001) (Table). Median OS was better in patients treated with a proteasome inhibitor triplet regimen vs VTD PACE-like combination (28.2 versus 12.6 months). OS was prolonged among patients who underwent any type of SCT compared with those who did not undergo SCT (44.0 versus 5.7 months, p&lt;0.001). Conclusions: This multicenter retrospective study is one of the largest PCL analyses performed to date and reveals the clinical practice patterns of treatment and survival of PCL patients across the U.S. in the novel treatment era. The survival analysis reinforces the poor prognosis in sPCL patients and the continued need for novel treatment approaches in this patient population. While limited by retrospective design, this analysis suggests prolonged survival with transplantation in both pPCL and sPCL. [Table: see text]
Report of a chronic myeloid leukemia registry in a low-and middle-income setting.
Authors: Nicolas Anthony Othieno-Abinya, Walter Mwanda, Miriam Claire Mutebi, Mary Flaviane Nyangasi, Valerian Mwenda, Peter Omondi Oyiro, Angela Awino Mcligeyo, Mohammed Shabbir Ezzi, Andrew Oluoch Odhiambo, Matilda Ong'ondi, Sitna Ali Mwanzi, Ebrahim Adamjee, Magdalene Induli
Journal: Journal of Clinical Oncology (2023)

7054 Background: Treatment of chronic myeloid leukaemia (CML) in Kenya has been supported since the year 2002 by a collaboration between the Max Foundation and Novartis Pharmaceuticals in the Glivec International Patient Assistance Program (GIPAP). In November 2020 this was transitioned to Max Access Solutions (MAS) that brought in the Ministry of Health as a partner. A broad range of BCR-ABL tyrosine kinase inhibitors are available. We wanted to describe epidemiology, treatment and outcome of CML in the country. Methods: Patients’ records were reviewed and data entered in a database. Key variables included age, sex, BMI, diet, disease phase at diagnosis, treatment, and outcome. Continuous variables were summarized using mean (standard deviation) or median (interquartile range). Categorical variables were summarized using counts and percentages. Bivariate comparisons of treatment outcome were done using chi-square or Fisher’s exact test. Analysis of variance (ANOVA) or Kruskal-Wallis test was used for continuous variables. Results: 1347 patients-males 748 (55.5%), females 599 (44.5%). Mean age was 44.5 years. Seventy (9.0%) were underweight, 88 (11.4%) obese. Mean body surface area (BSA) was 1.75m 2 . Chronic phase cases were 1177 (96.2%), accelerated phase 46 (3.8%), blastic phase 1 (0.1%). Mean bone marrow blast count was 5.25%, BCR-ABL/ABL was 63.7%, haemoglobin 10.8g/dl, total wbc count 225 x 10 9 /litre, platelets 392.5 x 10 9 /litre. Imatinib was administered upfront to 1319 patients (99.8%). Two hundred and six (15.3%) were switched to second line; 100 (48.8%) to dasatinib, 50 (24.4%) to bosutinib. Transformation was registered in 26 cases (1.9%) - accelerated in 13 (72.2%), blastic in 5 (27.8%), 4 (80.0%) being myeloid and 1 (20%) lymphoblastic. Those alive are 1151 (85.4%) and 185 (13.7%) lost to follow-up. Deaths were recorded in 11 (0.8%). Those with lower BSA were more likely to die (p = 0.01). Conclusions: CML in Kenya occurs at a younger age-group with a slight male preponderance. With availability of a range of BCR-ABL tyrosine kinase inhibitors, treatment outcome is close to what is documented in high-income settings.
Outcome of TP53-mutated CCUS and the risk of progression to myeloid neoplasms.
Authors: Syed Naseem Shah, Marissa Li, Anmol Baranwal, Dong Chen, Rong He, Hassan B. Alkhateeb, Ayalew Tefferi, Abhishek A Mangaonkar, Aref Al-Kali, Mrinal S Patnaik, Mithun Vinod Shah
Journal: Journal of Clinical Oncology (2023)

7059 Background: TP53-mutated ( TP53 mut ) myeloid neoplasms (MN) are aggressive leukemia with poor survival. A subset of TP53 mut MN is preceded by TP53 mut CCUS that is conventionally considered to be high-risk premalignant condition, though evidence supporting the notion is lacking. We studied outcomes of TP53 mut CCUS compared to TP53 wild-type ( TP53 wt ) CCUS. Methods: Mayo Clinic Molecular Hematology Database (N=7593) was queried to identify patients (pts) harboring pathogenic variant(s) in exons 4-11 of the TP53 gene with ≥2% variance allele frequency (VAF). CCUS was defined using the 5 th edition of the WHO Classification for MN. Results: Of 457 pts with TP53 mut , 29 (5.9%) had TP53 mut CCUS. The median age at diagnosis was 67 years, 17 (59%) were female, and 20 (69%) had received cytotoxic therapies. One and ≥2 TP53 mut were seen in 26 (89.6%) and 3 (10.3%) pts, respectively. Median TP53 mut VAF was 9% (range 3-42), 3 had TP53 mut VAF ≥20%, and 4 (14%) had non-MDS defining cytogenetic anomalies. Of 16 pts with available follow up evaluation (median interval 22 months, Table), 3 (10.3%) progressed to TP53 mut MN at 5, 13, and 14 months from diagnosis. We next compared outcomes of TP53 mut CCUS to TP53 wt CCUS (n=138). The proportion of pts developing MN was not different between TP53 wt and TP53 mut CCUS (18.1 vs 10.3%, P= .42). Progression free survival of TP53 mut CCUS was comparable to TP53 wt CCUS at 1- (77 vs 83%), 2- (67 vs 67%), and 5-years (67 vs 59%, P=.9). Similarly, overall survival of TP53 mut vs TP53 wt CCUS at 1- (81 vs 89%), 2- (76 vs 76%), and 5-years (76 vs 67%) was comparable ( P= .94). Conclusions: In contrast to the prevalent notion, TP53 mut was not associated with a higher risk of MN progression or mortality compared to TP53 wt CCUS. Majority of TP53 mut clones showed remarkable stability over years. [Table: see text]
A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy in survivors of cancer.
Authors: Ivana Lopez-Nieves, Christopher Chiang, Katherine Han, Lauren Piulson, Christina Seluzicki, Matthew Weitzman, Yi Lily Zhang, Iris Zhi, Ting Bao
Journal: Journal of Clinical Oncology (2023)

TPS12144 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect in cancer survivors that can last long after completion of neurotoxic chemotherapy. Patients with CIPN often experience neuropathy symptoms such as pain, tingling, numbness, paresthesia, and dysesthesia, which can lead to significant functional decline and diminished quality of life. This outcome highlights the importance of developing effective CIPN treatments to improve quality of life for this population. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Acupuncture is a widely used, minimally invasive Traditional Chinese Medicine technique that has shown promising evidence as an effective and safe treatment for CIPN. We hypothesize that acupuncture may reduce CIPN pain and improve overall CIPN symptoms in cancer survivors. Methods: We are conducting a two-arm, parallel randomized clinical trial comparing electroacupuncture (EA) versus sham acupuncture (SA) in cancer survivors. The EA arm includes ten sessions of EA over eight weeks using a standardized, semi-fixed protocol developed by our group. The SA arm includes a sham technique that uses a combination of non-acupuncture points and a non-insertion procedure in ten sessions over eight weeks. The primary outcome of this study is the Brief Pain Inventory-Short Form average pain item. The secondary outcomes are quantitative sensory testing measures and patient-reported outcomes that include the Neuropathic Pain Scale, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, CIPN-20, PROMIS Global Health Scale, and Patients' Global Impression of Change. The primary end point is week 12 and the secondary end point is week 24; treatment effects are assessed at baseline and at weeks 4, 8, 12, 18, and 24. The eligibility criteria includes: 1) Patients must be have no evidence of disease or have stable disease; 2) CIPN diagnosis with moderate-to-severe CIPN pain, defined by a score of 4 or greater on a scale 0-10 numerical scale rating; 3) completed neurotoxic chemotherapy at least three months prior; and 4) no changes in anti-neuropathy medications within three months of enrollment. As of February 2023, we have accrued 89 participants, with a total accrual target of 250 participants. Accrual completion is anticipated by December 2024. The demographic breakdown of our participants is as following: 71% white, 15% black or African American, 10% Asian, 3% more than one race, and 1% Native Hawaiian or Pacific Islander. 89% of the participants are non-Hispanic or Latino, 10% are Hispanic or Latino, and 1% are unknown. 71% of the participants are female and 29% are male. Clinical trial information: NCT04917796 .
RNA sequencing to characterize pathways in EGFR-mutated non-small cell lung cancer.
Authors: Nicole Yun, Ankur D Naqib, Jeffrey Allen Borgia, Marta Batus, Mary Jo J. Fidler
Journal: Journal of Clinical Oncology (2023)

e21019 Background: The purpose of our study is to explore patterns in gene expression for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Methods: 287 patients with EGFR-mutated lung cancer were identified using the Tempus Lens database. Raw RNA sequence expression data was requested from TEMPUS XT RNA analysis. Sequences were processed through the EdgeR analysis in the R programming environment. Differential abundance analysis was done to further filter out genes and Benjamini-Hochberg correction selected genes with a corrected p-value of &lt; 0.05 for further pathway analysis. Pathway analysis was performed using GSEA (Gene Set Enrichment Analysis). Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA Molecular Signatures Database (MsigDB) was performed for overexpressed and under-expressed genes in patients. Results: Pathway analysis run against the KEGG reference database and GSEA MSigDB helped to illustrate genes shared in activated and suppressed pathways in our patient cohort. For example, using the KEGG reference database, enriched pathways meeting p value significance threshold of &lt; 0.005 included the nicotine addiction, olfactory transduction, and cortisol synthesis and secretion pathways, amongst others. Suppressed pathways using the KEGG reference database meeting p value significance threshold of &lt; 0.005 included fat digestion and absorption, vitamin digestion and absorption, PPAR signaling pathway, and drug metabolism by cytochrome P450 and other enzymes. Using the GSEA MSigDB, enriched pathways included G protein-coupled receptor activity, sensory perception, synaptic signaling and trans-synaptic signaling, meanwhile suppressed pathways included cytolysis by host of symbiont cells, negative regulation of very-low-density lipoprotein particle remodeling, and oxidoreductase activity. Conclusions: Patterns in gene and pathway expression were observed in our cohort of patients with EGFR-mutated NSCLC. Analyzing RNA sequencing pathways showed differential up and down regulation of multiple pathways. For example, suppression of the fat and vitamin digestion and absorption pathways may shed light on processes involved in cancer cachexia and metabolism. Though further work needs to be done, RNA sequencing results for patients with EGFR-mutated lung cancer may lead to information on cancer development and additional therapeutic targets.
Mortality rate and social disparity trends with tyrosine kinase inhibitory availability in chronic myelogenous leukemia: An analysis in the US from 1999 to 2020.
Authors: Tony Varughese, Jamie Koprivnikar
Journal: Journal of Clinical Oncology (2023)

7055 Background: We analyzed CML mortality from 1999 to 2020 in the US in relation to FDA approval of tyrosine kinase inhibitors (TKIs). These agents were introduced in the 2000s, revolutionizing the treatment of CML and providing a paradigm for targeted therapy in oncology. Starting with imatinib in 2001, followed by dasatinib (2006), nilotinib (2007), and bosutinib (2012). TKIs have increased tolerability and efficacy for the treatment of CML as compared to previous treatment modalities. We investigated age-adjusted mortality rates (AAMR) and annual percent change (APC) in this population in relation to TKI approval. Methods: Using the CDC WONDER database, we examined mortality trends from 1999 to 2020 for CML in the US. AAMRs were calculated per 100,000 people and stratified by sex, race/ethnicity, and census region. AAMR groups were listed as pre-TKI era and 1 year post-FDA approval of different TKI agents. We computed the APC trends for the respective stratification with Joinpoint, a regression analysis program. Results: Between 1999 and 2020 there were 35,268 deaths from CML. In 1999, overall AAMR initially was 0.8, which improved to 0.5 by 2020 with a respective APC of -2.5%. In our subgroup analysis there was a consistent and significant decrease in AAMR since the introduction of Imatinib in 2001. With additional TKI releases, AAMR continued to decline in all subgroups. APC for mortality rates was similar between all subgroups [-2.0 to -2.8%] indicating a similar benefit regardless of subgroup. Male AAMR was consistently higher than female AAMR. Black and white patients (0.5, 2020) have a 2.5x higher AAMR (0.2, 2020) compared to Asian patients. Census region did not show a significant difference between each other. Conclusions: Since the FDA approval of imatinib in 2001 and the subsequent release of TKIs there has been a significant impact on reducing AAMR for patients with CML. The decline was seen in sex, race, and census region. The APCs were similar between all subgroups indicating a consistent improvement in survival. Possible etiologies of disparities in AARM for males in comparison to females and for black and white patients in comparison to Asian patients include gender and race-associated gene polymorphisms possibly inducing differences in drug metabolism. Further gender and race specific pharmacokinetic studies would be useful to further elucidate etiology of the disparity and may lead to changes in TKI dosing strategies. [Table: see text]
Distribution pattern of metastatic lymph nodes in 870 cases of nasopharyngeal carcinoma: A clue for individualized elective prophylactic neck irradiation.
Authors: Lei Wang, Zheng Wu, Qian He, Yiting Li, Subin Wang, Feiping Li, Hui Wang, Wenhui Li, Yaqian Han
Journal: Journal of Clinical Oncology (2023)

e18049 Background: We aimed to explore a potential individualized elective prophylactic neck irradiation (iEPNI) to optimize the current strategy by investigating the distribution of metastatic lymph nodes (LNs) in nasopharyngeal carcinoma (NPC). Methods: Magnetic resonance imaging (MRI) and clinical data of 870 non-distant metastatic NPC patients admitted to the Hunan Cancer Hospital between January 2019 and December 2019 were reviewed. All patients were staged using the 8 th TNM staging system, and the LNs location was assigned based on the 2013 guidelines. According to the distribution patterns of the LNs in NPC, the intra-regional lymphatic drainage levels were categorized into the following three stations: Station 1 st of level VIIa and II; Station 2 nd of level III and Va; and Station 3 rd of level IV, Vb, and Vc. Other levels were defined as extra-regional areas. Results: The incidence of LNs metastasis was 822/870 (94.5%), including 198 cases of unilateral metastasis and 624 cases of bilateral metastasis. Among the 870 patients, the most frequently involved intra-regional lymphatic drainage was level IIb (87.1%), followed by level VIIa (80.0%), IIa (61.8%), Va (30.6%), IV (21.4%), Vb (8.9%), and Vc (1.1%). In the extra-regional areas, the detailed LNs distribution was: level Ia (0.2%), level Ib (7.7%), level VI (0.1%), level VIIb (5.6%), level VIII (5.5%), level IX (0.3%), and level X (0.2%). The rates of LNs metastasis in Station 1 st , Station 2 nd , and Station 3 rd were 820/870 (94.3%), 532/870 (61.1%), and 199/870 (22.9%), respectively. Only 4 patients were considered to be skipping metastasis among the three stations (4/870, 0.5%). Additionally, in 203 patients with unilateral Station 1 st LNs metastasis, there were 86 (42.4%) and 37 (18.2%) patients with ipsilateral Station 2 nd and Station 3 rd metastasis, respectively, and 3 (1.5%) and 1 (0.5%) patients with contralateral Station 2 nd and Station 3 rd LNs metastasis, respectively. Conclusions: LNs spread from Station 1 st to Station 3 rd successively with rare skipping metastasis. A potential iEPNI strategy of prophylactical neck irradiation to the ipsilateral latter node-negative station might be feasible, which is detailed as follows: irradiation to Station 1 st in patients with no LNs metastasis, irradiation to Station 2 nd in patients with only Station 1 st metastasis, and irradiation to Station 3 rd in patients with Station 2 nd metastasis but without Station 3 rd metastasis. Further prospective investigations are expected to validate the strategy.
Disparities in African American oncology care in the US: A socioeconomic and geographic outlook.
Authors: Ranjit Jasaraj, Suman Gaire, Ekaterina Proskuriakova, Mohammed Azher Kassem, Paramjeet Grewal Khosla, Larissa Verda, Nabin R Karki
Journal: Journal of Clinical Oncology (2023)

e18590 Background: Mortality from cancer has been decreasing for all races and ethnicities. However, African Americans (AA) continue to have the highest mortality. Healthcare disparity contributes to poor outcomes. Here, we evaluate the differences in access to health care and socioeconomic status between different races and ethnicities in the US. Methods: We extracted data on demographic and healthcare coverage variables of patients diagnosed with cancer from the 2021 Behavioural Risk Factor Surveillance System (BRFSS), a national health-related telephone survey. We analyzed the effect of racial disparities in relation to socioeconomic factors and Census Bureau regions. R version 2.2.2 was used for all data extraction and analysis. Results: Out of 4,31,639 responders of BRFSS from the mainland US territory, 41,933 (9.71%) had been diagnosed with cancer other than skin cancer. Of these, 9,746 (9.74%) were from North East, 8,827 (9.11%) were from West, 10,806 (9.98%) were from South, and 12,554 (9.92%) were from Mid-West. In our sample, 35,137 (83.8%) were White, 2,356 (5.6%) were AA, 1,383 (3.3%) were Hispanic, and 3,047 (7.3%) were from others (Asian, American Indian/Alaskan Native, other race). More than 95% of oncology patients had health care coverage. However, the proportion of AA without healthcare coverage was higher than the White population (2.1% vs 1.2%, p &lt; 0.005). 5.3% of cancer patients did not see physicians due to cost. This percentage was significantly higher among AA compared to White (8.2% vs 4.3%, p &lt; 0.001). The rates of health care coverage and being unable to see a physician due to cost between AA and White were also statistically significant in each census region (not shown in table). Compared to White, AA patients with cancer were found to have statistically significantly lower education and income levels. This difference was present in all census regions of the US (not shown in table). Conclusions: Among cancer patients, AA are more likely not to have health care coverage, unable to see a physician due to cost, and have lower education and income level than White. These disparities impacting care of cancer patients exists in all major US regions, which likely promotes poor health outcomes. In addition, AA patients are underrepresented in this survey. [Table: see text]